The transition-metal catalyzed olefin metathesis reaction has emerged as an indispensable methodology for the construction of new carbon-carbon double bonds (see (a) Fürstner, A. Angew. Chem., Int. Ed. 2000, 39, 3013. (b) Trnka, T. M.; Grubbs, R. H. Acc. Chem. Res. 2001, 34, 18. (c) Schrock, R. R. Chem. Rev. 2002, 102, 145. (d) Schrock, R. R.; Hoveyda, A. H. Angew. Chem., Int. Ed. 2003, 42, 4592. (e) Vougioukalakis, G.; Grubbs, R. H. Chem. Rev. 2009, 110, 1746. (f) Samojlowicz, C.; Bieniek, M.; Grela, K. Chem. Rev. 2009, 109, 3708). Since its discovery in the 1950s, metathesis has been employed with great success in a number of fields, including biochemistry, materials science, and green chemistry (see (a) Binder, J. B.; Raines, R. T. Curr. Opin. Chem. Biol. 2008, 12, 767; (b) Leitgeb, A.; Wappel, J.; Slugovc, C. Polymer 2010, 51, 2927; (c) Sutthasupa, S.; Shiotsuki, M.; Sanda, F. Polym. J. 2010, 42, 905; (d) Liu, X.; Basu, A. J. Organomet. Chem. 2006, 691, 5148; (e) Schrodi, Y.; Ung, T.; Vargas, A.; Mkrtumyan, G.; Lee, C. W.; Champagne, T. M.; Pederson, R. L.; Hong, S. H. CLEAN Soil, Air, Water 2008, 36, 669). However, an ongoing challenge in cross metathesis (CM) reactions has been the control of stereoselectivity, as metathesis catalysts generally favor formation of the thermodynamically preferred E-olefin (see Grubbs, R. H. Handbook of Metathesis; Wiley-VCH: Weinheim, 2003). Many natural products and pharmaceutical targets, on the other hand, contain Z-olefins (see Cossy, J.; Arseniyadis, S.; Meyer, C. Metathesis in Natural Product Synthesis: Strategies, Substrates, and Catalysts, 1st ed.; Wiley-VCH: Weinheim, Germany, 2010). Recent groundbreaking work by Schrock and Hoveyda et. al. resulted in the development of the first Z-selective metathesis catalysts using molybdenum and tungsten, allowing for the effective synthesis of Z-olefins via metathesis for the first time and opening the door to the development of new and improved Z-selective catalysts (see (a) Flook, M. M.; Jiang, A. J.; Schrock, R. R.; Müller, P.; Hoveyda, A. H. J. Am. Chem. Soc. 2009, 131, 7962. (b) Marinescu, S. C.; Schrock, R. R.; Müller, P.; Takase, M. K.; Hoveyda, A. H. Organometallics 2011, 30, 1780. (c) Yu, M.; Wang, C.; Kyle, A. F.; Jukubec, P.; Dixon, D. J.; Schrock, R. R.; Hoveyda, A. H. Nature 2011, 479, 88. (d) Meek, S. J.; O'Brien, R. V.; Llaveria, J.; Schrock, R. R.; Hoveyda, A. H. Nature 2011, 471, 461. (e) Flook, M. M.; Ng, V. W. L.; Schrock, R. R. J. Am. Chem. Soc. 2011, 133, 1784. (f) Jiang, A. J.; Zhao, Y.; Schrock, R. R.; Hoveyda, A. H. J. Am. Chem. Soc. 2009, 131, 16630).
More recently, we reported on the synthesis and activity of a comparable class of Z-selective ruthenium metathesis catalysts (2, 3) containing a chelating N-heterocyclic carbene (NHC) ligand (Scheme 1) (see (a) Endo, K.; Grubbs, R. H. J. Am. Chem. Soc. 2011, 133, 8525. (b) Keitz, B. K.; Endo, K.; Herbert, M. B.; Grubbs, R. H. J. Am. Chem. Soc. 2011, 133, 9686. (c) Keitz, B. K.; Endo, K.; Patel, P. R.; Herbert, M. B.; Grubbs, R. H. J. Am. Chem. Soc. 2011, 134, 693). The Z-selective ruthenium-based metathesis catalyst, nitrato-catalyst 3, was found to possess turnover numbers (TONs) approaching 1000 and Z-selectivity on average around 90%. This catalyst has been shown to be effective for the synthesis of homo- and heterocross products, stereoregular polymers, and a variety of insect pheromones and macrocyclic musks (see (a) Keitz, B. K.; Endo, K.; Patel, P. R.; Herbert, M. B.; Grubbs, R. H. J. Am. Chem. Soc. 2011, 134, 693. (b) Keitz, B. K.; Fedorov, A.; Grubbs, R. H. J. Am. Chem. Soc. 2012, 134, 2040. (c) Herbert, M. B.; Marx, V. M.; Pederson, R. L.; Grubbs, R. H. DOI: 10.1002/anie.201206079. (d) Marx, V. M.; Herbert, M. B.; Keitz, B. K.; Grubbs, R. H. Unpublished results).

The Ru—C bond of the chelate in 2 and 3 is formed via an intramolecular C—H activation of an N-bound adamantyl group induced by the addition of silver pivalate (AgOPiv) (Scheme 1). Past experience with similarly activated complexes, combined with computational data, suggested that replacing the mesityl group of compound 3 with a N-2,6-diisopropylphenyl (DIPP) group would result in increased catalyst stability and selectivity. As detailed in a previous report, attempts to make significant alterations to the NHC substituents, both to the chelating group and to the N-aryl group, mostly resulted in decomposition upon exposure to AgOPiv (see Herbert, M. B.; Lan, Y.; Keitz, B. K.; Liu, P.; Endo, K.; Day, M. W.; Houk, K. N.; Grubbs, R. H. J. Am. Chem. Soc. 2012, 134, 7861).
Despite the advances achieved in preparing Z-selective metathesis catalysts, a continuing need in the art exists for improved catalysts, particularly Z-selective metathesis catalysts that provide higher turnover numbers (TONs) and improved Z-selectivity as well as improved methods for making such catalysts.